Systemic nicotine increased dopamine (DA) overflow in the n. accumbens in a stereoselective manner. Focal infusions of nicotine into the n. accumbens also increased DA in a dose-dependent fashion. The administra- tion of (-)nicotine but not (+)nicotine into the ventral tegmentum (VTA) increased DA overflow in both the VTA and n. accumbens. Extracellular DA in the frontal cortex and n. accumbens decreased following corticoste- rone, while there was no change in striatum. Serotonin also decreased in the frontal cortex, while norepinephrine (NE) showed a small transient increase. Corticosterone applied focally to the VTA also decreased n. accumbens DA. Systemic cocaine had little effect on extracellular NE in the frontal cortex or hippocampus of anesthetized rats. Focally applied cocaine increased NE in the hippocampus in a dose-dependent manner, but had lesser effects in the frontal cortex. In the awake rat, however, systemic cocaine increased NE in both the frontal cortex and hippocampus. Chronic fluoxetine produced an apparent subsensitivity in both the raphe and frontal cortex to focally applied or systemically administered fluoxetine. D1 dopamine agonists appear to increase striatal ACh direct- ly through striatal sites and not indirectly through the frontal cortex.